肥大细胞增多症,通常涉及皮肤和骨髓的肥大细胞的克隆增殖,具有从皮肤病变到全身性疾病的各种临床表现。对皮肤肥大细胞增多症进行对症治疗,但全身性肥大细胞增多症是针对突变受体酪氨酸激酶c-KIT的靶向治疗,肥大细胞增多症的致病驱动因素。然而,目前尚无对症治疗难治性皮肤肥大细胞增多症的治疗指南.我们在此报告了一种选择遗传知情疗法治疗有症状和顽固性皮肤肥大细胞增多症的方法。
■我们对一名患有顽固性皮肤肥大细胞增多症的23岁女性进行了激光捕获富集后的真皮肥大细胞的突变分析。分析揭示了在蛋白质c-KIT中的密码子816(D816V)突变处的天冬氨酸到缬氨酸的置换。基于这些结果,我们开始使用多激酶/KIT抑制剂midostaurin治疗,对D816Vc-KIT突变有效的治疗方法。治疗3个月后,患者表现为皮肤病变的数量和大小减少,报告瘙痒消退,其他肥大细胞相关症状的严重程度降低.
■肥大细胞增多症的治疗在很大程度上取决于疾病仅限于皮肤还是全身。然而,没有针对皮肤肥大细胞增多症的指南对症治疗没有反应.在本报告中描述了患有顽固性皮肤肥大细胞增多症的患者,我们描述了一种策略,其中皮肤突变分析用于指导靶向治疗的选择.
■在皮肤中进行肥大细胞突变分析为选择有症状和难治性皮肤肥大细胞增多症的靶向治疗提供了一种手段。
Mastocytosis, a clonal proliferation of mast cells commonly involving the skin and bone marrow, has a varied clinical presentation ranging from cutaneous lesions to systemic disease. Cutaneous mastocytosis is managed symptomatically, but systemic mastocytosis is treated with targeted therapy against the mutated receptor tyrosine kinase c-KIT, the pathogenic driver of mastocytosis. However, there are no guidelines for the treatment of cutaneous mastocytosis refractory to symptomatic management. We herein report a method to select genetically informed therapy for symptomatic and recalcitrant cutaneous mastocytosis.
UNASSIGNED: We performed a mutational analysis of dermal mast cells after enrichment by laser capture in a 23-year-old woman with recalcitrant cutaneous mastocytosis. The analysis revealed a aspartic acid to valine substitution at codon 816 (D816V) mutation in the protein c-KIT. Based on these results, we initiated treatment with the multi-kinase/KIT inhibitor midostaurin, a treatment effective against the D816V c-KIT mutation. After 3 months of treatment, the patient exhibited a reduction in the number and size of cutaneous lesions and reported resolution of pruritus and decreased severity of other mast cell-related symptoms.
UNASSIGNED: The treatment of mastocytosis relies heavily on whether the disease is limited to the skin or systemic. However, there are no guidelines for cutaneous mastocytosis that does not respond to symptomatic management. In the present report describing a patient with recalcitrant cutaneous mastocytosis, we describe a strategy in which skin mutational analysis is used to guide the selection of targeted therapy.
UNASSIGNED: Performing mast cell mutational analyses in the skin provides a means to select targeted therapy for symptomatic and refractory cutaneous mastocytosis.